Nitro-fatty acids are electrophilic anti-inflammatory mediators which are generated during myocardial ischemic injury. Whether these species exert anti-arrhythmic effects in the acute phase of myocardial ischemia has not been investigated so far. The group of Martin Mollenhauer et. al demonstrate that pretreatment of mice with 9- and 10-nitro-octadec-9-enoic acid (nitro-oleic acid, NO2-OA) significantly reduced the susceptibility to develop acute ventricular tachycardia (VT). Accordingly, epicardial mapping revealed a markedly enhanced homogeneity in ventricular conduction. NO2-OA treatment of isolated cardiomyocytes lowered the number of spontaneous contractions upon adrenergic isoproterenol stimulation and nearly abolished ryanodine receptor type 2 (RyR2)-dependent sarcoplasmic Ca2+ leak. NO2-OA also significantly reduced RyR2-phosphorylation by inhibition of increased CaMKII activity. Thus, NO2-OA might be a novel pharmacological option for the prevention of VT development.
Publication: Mollenhauer M, Mehrkens D, Klinke A, Lange M, Remane L, Friedrichs K, Braumann S, Geißen S, Simsekyilmaz S, Nettersheim FS, Lee S, Peinkofer G, Geisler AC, Geis B, Schwoerer AP, Carrier L, Freeman BA, Dewenter M, Luo X, El-Armouche A, Wagner M, Adam M, Baldus S, Rudolph V.
Nitro-fatty acids suppress ischemic ventricular arrhythmias by preserving calcium homeostasis. Sci Rep. 2020 Sep 18;10(1):15319. doi: 10.1038/s41598-020-71870-6. PMID: 32948795.